von Willebrand Disease (VWD) Testing Interpretations
Guidance For Your VWD Results
Versiti Diagnostic Labs is proud to continue expanding the frontier of von Willebrand Disease diagnostics through advanced and comprehensive laboratory medicine. In order to best support proivders in their patients' diagnostic journeys, please review the below assay descriptions and test result interpretations.
For questions related to VWD test result interpretation, please contact Versiti Client Services at 800-245-3117 x 6250, or Labinfo@versiti.org to be put in contact with our Hemostasis laboratory team.
VWD is the most common autosomal inherited bleeding disorder, with an estimated prevalence of 1 in 1000 individuals. Classification of VWD is currently based on the criteria developed by the VWF subcommittee of the International Society on Thrombosis and Haemostasis (ISTH) and the National Institutes of Health National Heart, Lung, and Blood Institute (NHLBI) VWD expert panel. Inherited VWD is classified into 3 major categories: partial quantitative VWF deficiency (type 1), complete deficiency (type 3), and qualitative deficiency (type 2). Type 2 is further classified into subtypes defined by defects in multimerization (type 2A), increased platelet binding (type 2B and platelet-type VWD), defects in VWF-platelet binding or VWF:CB not attributable to multimer defects (type 2M), or defects in factor VIII (FVIII) binding (type 2N). Type 1 is the most common, accounting for about 85% of VWD, whereas type 3 is the least common, affecting an estimated 1 in 1 million individuals. Type 2 VWD is less common than type 1.
Diagnosis of VWD includes:
- Assessment of history of bleeding symptoms;
- Assessment of family history of bleeding or VWD; and
- Confirmatory laboratory testing.
It is suggested that assessment of personal and family history includes use of validated bleeding assessment tools by the ISTH. A panel of three studies (VWF antigen, VWF platelet-binding activity, and Factor VIII activity) is the recommended minimum panel of studies to obtain as the initial laboratory evaluation of a patient for VWD. Quantitative VWF levels less than 50 IU/dL are associated with increased bleeding risk per the NHLBI, while levels less than 30 IU/dL are diagnostic of VWD. The most recent recommendations allow treatment of patients with VWF levels between 30 and 50 IU/dL who have bleeding symptoms.
|Normal||Type 1||Type 1C||Type 2A||Type 2B*||Type 2M||Type 2N||Type 3|
|VWF:Ag||N||↓↓||↓↓||N or ↓|
|N or ↓|
|↓ or ↓↓||N or ↓||Absent|
VWF:RCo/VWF:Ag, VWF:GPIbM/VWF:Ag, VWFGPIbR/VWF:Ag
|N||N||N||↓↓||↓ or ↓↓||↓↓||N||N/A|
|Platelet Count||N||N||N||N||N or ↓||N||N||N|
|VWFpp/VWF:Ag||N||N||↑ or ↑↑||N or ↑||↓HMW||N||N||N/A|
|VWF:CB-III/VWF:Ag||N||N||N||↓↓||↓ or ↓↓||N or ↓||N||N/A|
N = Normal; ↓ = Reduced; ↓↓ = Markedly reduced; ↑ = Increased; ↑↑ = Markedly increased; LD-RIPA = Low-dose ristocetin-induced platelet aggregation; HMW = High molecular weight; N/A = not assessable but to absense of VWF antigen.
- Type 1 = low levels of VWF
- Type 3 = absent VWF (autosomal recessive)
- Type 2A = loss of function attributable to multimerization defects
- Type 2B = gain of function-platelet binding
- Type 2M = loss of function-platelet or collagen binding with normal multimers
- Type 2N = loss of function-FVIII binding(autosomal recessive)
This assay is designed to distinguish type 2N von Willebrand disease (an autosomal recessive disorder) from mild hemophilia A and hemophilia A carriers. Patient VWF is captured with monoclonal antibody in a microtiter well, any patient-derived FVIII:C is washed away and recombinant FVIII is then added. Patient-derived VWF antigen is quantitated immunologically, the bound FVIII is quantitated by chromogenic assay, and assay results are reported as the ratio of FVIII to VWF. Comparison is made to the results obtained with well-defined control plasmas (either compound type 1/type 2N VWD, 2N carrier state or normal). Numerical results and an interpretation are provided.
A ratio near 1.0 is observed for normal samples, vary low ratios are observed for samples obtained from patients with type 2N VWD. Intermediate ratios are observed for heterozygous carriers of type 2N VWD.
- Sadler JE, Budde U, Eikenboom JC, et al; Working Party on von Willebrand Disease Classification. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost. 2006;4(10):2103-2114.
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- Slobodianuk TL, Kochelek C, Foeckler J, Kalloway S, Weiler H, Flood VH. Defective collagen binding and increased bleeding in a murine model of von Willebrand disease affecting collagen IV binding. J Thromb Haemost 2019; 17: 63–71.